Isoproterenol‐induced heart failure in the rat is associated with nitric oxide‐dependent functional alterations of cardiac function

Abstract

AimsThe role of nitric oxide (NO) in heart failure (HF) is complex and remains controversial. We tested the hypothesis that the role of NO in isolated atria and cardiomyocytes is altered in isoproterenol-induced HF. Methods and resultsRats received isoproterenol (ISO, 5 mg/kg/day, intraperitoneally) or vehicle for 1 week. Haemodynamic parameters were obtained by left ventricular catheterization. Effects of NOS inhibition on isolated atria and on electrically paced left ventricular myocytes were determined. Additionally, expressions of nitric oxide synthases and their allosteric modulators hsp90, caveolin-1, and caveolin-3 proteins in the left ventricles were measured. ISO increased left ventricular mass by 33% and decreased indices of left ventricular systolic and diastolic function dp/dt min and dp/dt max (both P , 0.05). Isolated atria from HF rats had a lower spontaneous beating rate (P , 0.05). NOS inhibition by L-NAME increased basal frequency and attenuated the positive chronotropic effect of beta-adrenergic stimulation in the HF group (P , 0.05). Ventricular myocytes from failing hearts had impaired cell shortening. L-NAME decreased contractility of control, but not failing myocytes. Left ventricular expressions of eNOS, hsp90, iNOS, but not nNOS or caveolins, were increased. ConclusionDespite the increased capacity for NO synthesis in isoproterenol-induced HF, NO does not sustain contractility of failing myocytes. NO may contribute to the decreased basal heart rate and it may accelerate beta-adrenergic stimulation of chronotropy.--

Role of Nitric Oxide in Isoproterenol-Induced Myocardial Infarction

“…In contrast, iNOS is a cytokine-inducible isoenzyme. In healthy heart, physiological amounts of NO may help to sustain cardiac inotropy [Krenek et al, 2009]. It is our hypothesis that in the ISO-induced MI model, the hypotensive effect observed after ISO administration, in the preinfarct stage [Chagoya de Sánchez, 1997], is mediated by NO and might be critical for the MI development.…”

Common biomarkers of oxidative stress do not reflect cardiovascular dys/function in rats

“…Coronary heart disease accounts for more than 40% of cardiovascular deaths and its most serious form, acute myocardial infarction (AMI), is the principal cause of chronic heart failure 1 . Elevated catecholamines are known risk factors for a cardiovascular event and the synthetic catecholamine, isoprenaline has been used for about a half a century for inducing AMI and subsequent heart failure in small laboratory animals [7][8][9][10] . In our previous study, we found in a very small number of animals some correlations among various parameters in healthy and AMIinduced animals 10 .…”

Metformin Inhibits Isoproterenol-induced Cardiac Hypertrophy in Mice

“…Moreover, adrenergic agonists such as isoproterenol can induce cardiac hypertrophy in experimental animals [6][7][8]. Isoproterenol-induced cardiac hypertrophy is a reliable, reproducible, and well-characterized model of pathological cardiac hypertrophy [9,10].…”